[A fractured kidney, an unexpected sequela of a remote lumbar trauma]. / Un rein fracturé, séquelle inattendue d'un ancien traumatisme lombaire.

A 40-year old man is evaluated for arterial hypertension of one's year duration, which responded well to salt restriction and mild antihypertensive medication. The standard investigation for possible secondary hypertension is negative. In view of a remote history of left renal trauma, it is decided to do an angiogram, which reveals the presence of a fractured left kidney. This unusual image is considered to be secondary to the combination of an arterial supply provided by two polar arteries and of scarring in the mid-portion of the renal parenchyma secondary to the remote trauma.

Mesenchymal stromal cells genetically engineered to overexpress IGF-I enhance cell-based gene therapy of renal failure-induced anemia.

We previously demonstrated that erythropoietin (EPO)-secreting mesenchymal stromal cells (MSC) can be used for the long-term correction of renal failure-induced anemia. The present study provides evidence that coimplantation of insulin-like growth factor I (IGF-I)-overexpressing MSC (MSC-IGF) improves MSC-based gene therapy of anemia by providing paracrine support to EPO-secreting MSC (MSC-EPO) within a subcutaneous implant. IGF-I receptor RNA expression in murine MSC was demonstrated by RT-PCR. Functional protein expression was confirmed by immunoblots and MSC responsiveness to IGF-I stimulation in vitro. IGF-I was also shown to improve MSC survival following staurosporin-induced apoptosis in vitro. A cohort of C57Bl/6 mice was rendered anemic by right kidney electrocoagulation and left nephrectomy. MSC-EPO were subsequently admixed in a bovine collagen matrix and implanted, in combination with MSC-IGF or MSC null, by subcutaneous injection in renal failure mice. In mice receiving MSC-EPO coimplanted with MSC-IGF, hematocrit elevation was greater and enhanced compared with control mice; heart function was also improved. MSC-IGF coimplantation, therefore, represents a promising new strategy for enhancing MSC survival within implanted matrices and for improving cell-based gene therapy of renal anemia.

[Indinavir-associated tubulointerstitial renal disease]. / Néphropathie tubulo-interstitielle associée à l'indinavir.

Indinavir, used for the treatment of HIV disease, forms distinctive crystals in the urine. The crystalluria has been associated principally with several urinary tract abnormalities which may require discontinuation of the drug. We present a case of progressive leucocyturia and renal impairment occurring during indinavir treatment which illustrates vividly the impact of the crystalluria on the tubulointerstitial renal compartment.

Erythropoietin delivery by genetically engineered bone marrow stromal cells for correction of anemia in mice with chronic renal failure.

The goal of this research was to develop a strategy to couple stem cell and gene therapy for in vivo delivery of erythropoietin (Epo) for treatment of anemia of ESRD. It was shown previously that autologous bone marrow stromal cells (MSCs) can be genetically engineered to secrete pharmacologic amounts of Epo in normal mice. Therefore, whether anemia in mice with mild to moderate chronic renal failure (CRF) can be improved with Epo gene-modified MSCs (Epo+MSCs) within a subcutaneous implant was examined. A cohort of C57BL/6 mice were rendered anemic by right kidney electrocoagulation and left nephrectomy. In these CRF mice, the hematocrit (Hct) dropped from a prenephrectomy baseline of approximately 55% to 40% after induction of renal failure. MSCs from C57BL/6 donor mice were genetically engineered to secrete murine Epo at a rate of 3 to 4 units of Epo/10(6) cells per 24 h, embedded in a collagen-based matrix, and implanted subcutaneously in anemic CRF mice. It was observed that Hct increased after administration of Epo+MSCs, according to cell dose. Implants of 3 million Epo+MSCs per mouse had no effect on Hct, whereas 10 million led to a supraphysiologic effect. The Hct of CRF mice that received 4.5 or 7.5 million Epo+MSCs rose to a peak 54+/-4.0 or 63+/-5.5%, respectively, at 3 wk after implantation and remained above 48 or 54% for >19 wk. Moreover, mice that had CRF and received Epo+MSCs showed significantly greater swimming exercise capacity. In conclusion, these results demonstrate that subcutaneous implantation of Epo-secreting genetically engineered MSCs can correct anemia that occurs in a murine model of CRF.

Anti-erythropoietin antibody-mediated pure red cell aplasia after treatment with recombinant erythropoietin products: recommendations for minimization of risk.

Since 1998, there has been a marked increase in incidence of pure red cell aplasia secondary to development of anti-erythropoietin antibodies (Ab+ PRCA) in patients who have chronic kidney disease (CKD) and receive recombinant erythropoietin. The relationship between incidence of Ab+ PRCA and specific erythropoietin products has not been examined rigorously. Manufacturers provided data regarding exposure to erythropoietin products and incidence of Ab+ PRCA between January 1998 and March 2003 in patients with CKD. Assuming a Poisson distribution, a maximum likelihood estimate for the Poisson rate parameter was calculated for each product. A test for homogeneity of Poisson rates was conducted to compare likelihood estimates between products. Global incidence of Ab+ PRCA was relatively low. Likelihood estimates were not significantly different for Epogen, Procrit, and Aranesp, independent of their formulation or route of administration. Eprex lacking human serum albumin (HSA) and administered subcutaneously was associated with the greatest risk of Ab+ PRCA. HSA-containing Eprex administered subcutaneously was associated with a lower risk than HSA-free Eprex administered subcutaneously, but this risk exceeded that of intravenous Epogen and intravenous HSA-free Eprex. NeoRecormon administered subcutaneously was associated with less risk than subcutaneous HSA-free Eprex but more risk than intravenous Epogen. HSA-free Eprex should not be administered subcutaneously to patients with CKD due to increased risk of Ab+ PRCA. Although the subcutaneous administration of HSA-containing Eprex is riskier than intravenous Epogen and intravenous HSA-free Eprex, and the use of subcutaneous NeoRecormon is riskier than intravenous Epogen, there is currently no evidence that other products are safer.

The persisting pneumatoenteric recess and the infracardiac bursa: possible role in the pathogenesis of right hydrothorax complicating peritoneal dialysis.

Hydrothorax, an uncommon complication of peritoneal dialysis (PD), results from the migration of dialysis fluid under pressure from the peritoneal cavity into the pleural space. The exact site of the transdiaphragmatic fluid leak remains obscure, but the right-sided predominance of the hydrothorax points to the presence of abnormalities in the right hemidiaphragm. Such abnormalities have occasionally been described. In a recent case of acute massive right hydrothorax at the start of PD, the autopsy revealed extensive changes of amyloidosis that were comparable in both hemidiaphragms, prompting us to revisit the accepted explanation for right hydrothorax. We propose that an embryonic remnant--namely, the persisting pneumatoenteric recess and the infracardiac bursa--provides a passage connecting the peritoneal cavity to the right pleural space. The potential presence of this mechanism is consistent with the recognized clinical features of right hydrothorax complicating PD. This proposed route for dialysis fluid to form a right hydrothorax during PD can be investigated by currently available high-definition imaging techniques. This novel mechanism may also be involved in the pathogenesis of right hydrothorax observed in other medical conditions with tense ascites (liver cirrhosis, Meigs syndrome).

Attenuation of the alcohol preference of C57BL/6 mice during chronic renal failure.

The C57BL/6 inbred mouse strain is known for its strong, genetically determined preference for alcohol over water. In this study we examined the voluntary alcohol consumption (VAC) of C57BL/6 mice during chronic renal failure (CRF). Two weeks after the surgical induction of renal failure, CRF mice, together with normal and sham-operated control mice, were submitted to a standard 24-day VAC protocol. The mice were offered water for the first 6 days (period of acclimatization), alcohol (10% ethanol solution) for the next 4 days (period of forced alcohol exposure), and a choice between water and alcohol for the last 14 days (VAC period). The results (mean +/- SEM) obtained from the last 8 days of the VAC period were significantly different (P <.05) between CRF mice and the 2 control groups. As expected, CRF mice had a higher total fluid intake than did normal and sham-operated controls (9.5 +/- 0.2 vs 5.4 +/- 0.2 and 5.4 +/- 0.2 g/d). Surprisingly, despite their increased total fluid consumption, CRF mice nearly abolished their absolute alcohol intake compared with that of both control groups (3.2 +/- 0.5 vs 13.1 +/- 0.8 and 14.2 +/- 1.1 g alcohol/kg body wt/d). The resulting alcohol preference ratio (g alcohol/g total fluid) was markedly decreased in the CRF mice compared with that in both control groups (0.09 +/- 0.01 vs 0.62 +/- 0.03 and 0.64 +/- 0.05). We conclude that the innate alcohol preference of C57BL/6 mice is nearly abolished during CRF. Additional studies to clarify the mechanism of this striking change in drinking pattern are required, with special emphasis on the possible role of angiotensin II, which is involved in thirst regulation and known to reduce the alcohol consumption of normal alcohol-preferring rats.